Researchers from FFUP and IPO Porto reveal new discoveries in the metabolomic signature of renal cell carcinoma

In recent years, the research group at UCIBIO - Laboratory of Toxicology, Faculty of Pharmacy, University of Porto - has focused on studying metabolic reprogramming in urological cancers to identify potential biomarkers with different clinical applications, including diagnosis, prognosis, and response to treatment. The most recent study aimed to characterise the metabolic signature of renal cell carcinoma (RCC) by analysing the metabolome of renal tumour and adjacent non-tumour tissues, as well as urine samples collected from the same patients. This work was conducted in collaboration with the Portuguese Institute of Oncology of Porto (IPO Porto).

The research team identified significant changes in the levels of 28 metabolites involved in different metabolic pathways in RCC tissue. In particular, a decrease in the levels of several amino acids and an increase in glucose and lactate were observed, highlighting the ‘Warburg effect’, in which tumour cells switch from oxidative phosphorylation to glycolysis for energy production. Alterations were also observed in the levels of six metabolites that participate in lesser known pathways of metabolic reprogramming in RCC, such as arginine biosynthesis, β-alanine metabolism and purine and pyrimidine metabolism. The metabolites altered in the tumoral tissue showed statistically significant correlations with certain metabolites present in the urine of the same patients. This is a promising finding that suggests that urine analysis can provide a non-invasive way of diagnosing and monitoring the response to treatment in RCC patients.

Authors and Affiliations:

Filipa Amaro, Maria de Lourdes Bastos, Paula Guedes de Pinho, Joana Pinto: UCIBIO, Departamento de Ciências Biológicas, Laboratório de Toxicologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal & Associate Laboratory Institute for Health and Bioeconomy - i4HB, Universidade do Porto, Porto, Portugal

Márcia Carvalho: FP-I3ID, FP-BHS, Universidade Fernando Pessoa, Porto, Portugal & Faculdade de Ciências da Saúde, RISE-UFP, Universidade Fernando Pessoa, Porto, Portugal

Carina Carvalho-Maia, Carmen Jerónimo, Rui Henrique: Epigenética & Biologia do Cancro, Centro Compreensivo de Cancro do Porto Raquel Seruca (Porto.CCC), Instituto Português Oncologia do Porto Francisco Gentil, E.P.E. (IPO Porto), Porto, Portugal

Abstract:

Introduction: Despite considerable advances in cancer research, the increasing prevalence and high mortality rate of clear cell renal cell carcinoma (ccRCC) remain a significant challenge. A more detailed comprehension of the distinctive metabolic characteristics of ccRCC is vital to enhance diagnostic, prognostic, and therapeutic strategies.

Objectives: This study aimed to investigate the metabolic signatures of ccRCC tumours and, for the first time, their correlation with the urinary metabolome of the same patients.

Methods: We applied a gas chromatography-mass spectrometry (GC-MS)-based metabolomic approach to analyse matched tissue and urine samples from a cohort of 18 ccRCC patients and urine samples from 18 cancer-free controls. Multivariate and univariate statistical methods, as well as pathway and correlation analyses, were performed to assess metabolic dysregulations and correlations between tissue and urine.

Results: The results showed a ccRCC metabolic signature characterized by reprogramming in amino acid, energy, and sugar and inositol phosphate metabolisms. Our study identified, for the first time, significantly decreased levels of asparagine, proline, gluconate, 3-aminoisobutanoate, 4-aminobutanoate and urea in ccRCC tumours, highlighting the involvement of arginine biosynthesis, β-alanine metabolism and purine and pyrimidine metabolism in ccRCC. The correlations between tissue and urine metabolomes provide evidence for the potential usefulness of urinary metabolites in understanding systemic metabolic changes driven by RCC tumours.

Conclusions: These findings significantly advance our understanding of metabolic reprogramming in ccRCC and the systemic metabolic changes associated with the disease. Future research is needed to validate these findings in larger cohorts and to determine their potential implications for diagnosis and targeted therapies.

Journal: Metabolomics 2025 21:26

Link: https://doi.org/10.1007/s11306-024-02212-0